As of the census[9] of 2000, there were 11,800 people, 4,711 households, and 3,330 families residing in the county. The population density was 24 people per square mile (9/km²). There were 5,656 housing units at an average density of 11 per square mile (4/km²). The racial makeup of the county was 98.30% White, 0.13% Black or African American, 0.25% Native American, 0.29% Asian, 0.20% from other races, and 0.83% from two or more races. Approximately 0.56% of the population were Hispanic or Latino of any race.

There were 4,711 households out of which 31.20% had children under the age of 18 living with them, 57.40% were married couples living together, 10.10% had a female householder with no husband present, and 29.30% were non-families. 25.90% of all households were made up of individuals and 14.30% had someone living alone who was 65 years of age or older. The average household size was 2.46 and the average family size was 2.93.

In the county the population was spread out with 24.60% under the age of 18, 7.90% from 18 to 24, 26.30% from 25 to 44, 23.30% from 45 to 64, and 18.00% who were 65 years of age or older. The median age was 39 years. For every 100 females there were 92.10 males. For every 100 females age 18 and over, there were 87.70 males.

The median income for a household in the county was $30,421, and the median income for a family was $37,474. Males had a median income of $27,670 versus $15,909 for females. The per capita income for the county was $15,825. About 12.80% of families and 17.20% of the population were below the poverty line, including 22.60% of those under age 18 and 16.20% of those age 65 or over.

According to the Association of Religion Data Archives County Membership Report (2000), Madison County is a part of the Bible Belt with evangelical Protestantism being the majority religion. The most predominant denominations among residents in Madison County who adhere to a religion are Southern Baptists (37.87%), Independent/Non-Charismatic Churches (17.42%), and National Association of Free Will Baptists (12.10%).

At the presidential level, Madison County is a fairly independent county or battleground. Unlike many rural counties which tend to be Republican strongholds, voters in Madison County have seldom been lockstep in their voting tendencies. While George W. Bush carried Madison County both times in 2000 and 2004, Bill Clinton also carried the county both times in 1992 and 1996. Like many rural counties in Missouri in 2008, voters in Madison County favored John McCain over Barack Obama, although not as strongly as most of the other rural counties throughout the state.

Like most rural areas, voters in Madison County generally adhere to socially and culturally conservative principles which strongly influence their Republican leanings. In 2004, Missourians voted on a constitutional amendment to define marriage as the union between a man and a woman—it overwhelmingly passed Madison County with 84.78 percent of the vote. The initiative passed the state with 71 percent of support from voters as Missouri became the first state to ban same-sex marriage. In 2006, Missourians voted on a constitutional amendment to fund and legalize embryonic stem cell research in the state—it failed in Madison County with 57.60 percent voting against the measure. The initiative narrowly passed the state with 51 percent of support from voters as Missouri became one of the first states in the nation to approve embryonic stem cell research. Despite Madison County’s longstanding tradition of supporting socially conservative platforms, voters in the county have a penchant for advancing populist causes like increasing the minimum wage. In 2006, Missourians voted on a proposition (Proposition B) to increase the minimum wage in the state to $6.50 an hour—it passed Madison County with 74.43 percent of the vote. The proposition strongly passed every single county in Missouri with 75.94 percent voting in favor as the minimum wage was increased to $6.50 an hour in the state. During the same election, voters in five other states also strongly approved increases in the minimum wage.